study of brexucabtagene autoleucel plus dasatinib in adults with acute lymphoblastic leukemia

Conditions: Lymphoblastic Leukemia

Summary: to assess the feasibility of oral dasatinib pulses (3 consecutive days per week) during the first month following infusion of brexucabtagene autoleucel (tecartus) in adults with relapsed or refractory b-cell acute lymphoblastic leukemia.


Eligibility criteria:
inclusion criteria: * relapsed or refractory b-precursor all defined as one of the following: * primary refractory disease (\>=5% blasts or persistent extramedullary disease following induction therapy) * first or later relapse of marrow or extramedullary disease * persistence of mrd defined as detectable all by flow cytometry, pcr, or next-generation sequencing * relapsed or refractory disease after allogeneic transplant provided individual is at least 100 days from transplant at time of enrollment * patients with isolated, asymptomatic cns relapse will be eligible * age \>=18 years * eastern cooperative oncology group (ecog) performance status of 0-2 * adequate renal, hepatic, pulmonary and cardiac function defined as: * creatinine clearance (as estimated by cockcroft gault) ≥ 60 cc/min * serum alanine aminotransferase (alt)/aspartate aminotransferase (ast) ≤ 2.5 x upper limit of normal (uln) * total bilirubin ≤ 1.5 mg/dl, except in individuals with gilbert's syndrome. * cardiac ejection fraction ≥ 50%, no evidence of clinically significant pericardial effusion, and no clinically significant arrhythmias * baseline oxygen saturation \> 92% on room air * qtc ≤ 500ms * in individuals previously treated with blinatumomab, cd19 tumor expression in bone marrow or peripheral blood by flow cytometry or extramedullary site by ihc or flow cytometry * negative serum or urine beta-hcg test in females of childbearing potential within 3 weeks of enrollment * subjects of childbearing or child fathering potential must be willing to practice birth control from the time of enrollment on this study page 10 of 83 version 1.0 dated 27-april-2023 and for six (6) months after receiving the preparative conditioning regimen. * must be able to give informed consent. legal authorized representative (lar) is permitted if subject is cognitively able to provide verbal assent. exclusion criteria: * history of dasatinib intolerance * known sensitivity or allergy to aminoglycosides or any agents/reagents used in this study * blast count \> 75% in the bone marrow. * history of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 2 years * presence of cns-3 disease with neurological changes * history or presence of any cns disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage with clinical signs or symptoms * history of concomitant genetic syndrome such as fanconi anemia, kostmann syndrome, shwachman-diamond or any known bone marrow failure syndrome * history of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment * primary immunodeficiency * known infection with hiv, hepatitis b (hbsag positive) or untreated hepatitis c virus * presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring iv antimicrobials for management. * salvage chemotherapy including tkis for ph+ all within 1 week prior to enrollment * pregnant or breast feeding * patients with known autoimmune disease requiring the use of systemic immunosuppressive therapy within the last year * corticosteroid therapy within 7 days prior to enrollment * acute or chronic gvhd requiring systemic treatment within 4 weeks prior to enrollment * live vaccine ≤ 4 weeks prior to enrollment * any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment

Keywords: leukemia car t cell therapy brexucabtagene autoleucel dasatinib